Studies on sustained-release of active ingredients using hydrophobic polymers as carriers of formulations to achieve long-acting effects of medicines, relief of side effects, decrease in frequency of administration, or the like, have been conducted. To control release-rates of active ingredients is one of the most important subjects in these studies, and modifications of the form or the structure of formulations, usage of additives, and so on, have been tried to attain the controlled release [U.S. Pat. No. 3,279,996, Contraception, 27(5), 483-495, 1983, Japanese Patent Publication (kokai) No. 45694/1980, Japanese Patent Publication (kokai) 174007/1987, WO95/17881].
In case of the formulations for in vivo implantation containing hydrophobic polymers in which slightly soluble active ingredients are dispersed, the amount of the released active ingredients during a defined time period is smaller due to the low solubility of the active ingredients in the surrounding body fluid, and therefore, the formulations could not attain an acceptable efficacy of the active ingredients. With respect to such formulations as those containing the active ingredients dispersed in the hydrophobic polymers, and decreasing in the release rate of the active ingredients, the methods for controlling the release rate of the active ingredients, which comprise using, as an additive, mineral oil, glycerol, alcohol, or the like have been reported (Proceed. Intern. Symp. Control. Rel. Bioact. Mater, 14, 223-224(1987), Proceed. Intern. Symp. Control Rel. Bioact. Mater., 12, 145-146(1985), and Japanese Patent Publication (kokai) No. 100315/1980). The key underlying these methods is to disperse an amphiphilic solvent such as mineral oil, glycerol, or alcohol into the polymers together with the slightly soluble active ingredients to ensure the solubility and the released amount of the active ingredients to be increased. However, the formulations according to these methods may provide diverse release rates, depending on a combination among the slightly soluble ingredients, the additives, and the hydrophobic polymers, and, therefore, are limited to certain practical user.
In case of active ingredients such as live vaccines and inactivated vaccines, which are neither soluble in an organic solvent nor in water, it has been unknown if the active ingredients could be released from the hydrophobic polymer.